[ACE inhibition and atherosclerosis in the animal model]

The goals of rational antihypertensive medication should embrace the alleviation of atherosclerosis, the clinical consequences of which pose a major health problem and hence socio-economic concern for industrialized countries. Angiotensin converting enzyme (ACE) inhibitors are endowed with pharmacodynamic features which may help to attain this aim. Various animal experiments with cholesterol-fed rabbits, pigs and monkeys, as well as with rabbits with inherent disorder of lipid metabolism (WHHL-rabbit), demonstrated endothelial protection against loss of function due to hyperlipidemia and attenuation of lipid deposition in conduit blood vessels with ACE-inhibition. The alleviation of progressive atherosclerosis, which is a common feature of restenosis development following angioplasty, was shown in hypercholesterolemic rabbits and normal rats, but did not occur in clinically more relevant porcine models nor in large clinical trials. Circumstantial evidence from miscellaneous experiments is in line with the view that it is enhancement of bradykinin activity which causes the endothelial protection against the consequences of hypercholesterolemia. Furthermore, loss of relaxation of coronary resistance vessels without overt atherosclerosis despite hypercholesterolemia can be restored by augmentation of the EDRF-pathway as has been demonstrated with ramiprilat in vitro. This is being substantiated in preliminary clinical reports with different ACE-inhibitors. The possible association between improvement in both insulin sensitivity and endothelial function requires further investigation. The critical analysis of present experimental findings on a beneficial influence on both the spontaneous and the progressive development of atherosclerosis indicates ACE-inhibition to be more likely to preserve or restore the function of an intact endothelium than to interfere with the complex reaction occurring after injury of an already affected blood vessel.